ArticlePloS one2018
P38 MAPK inhibition prevents polybrene-induced senescence of human mesenchymal stem cells during viral transduction.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- Endometrial senescence: inevitability and conditional occurrence in female fertility.Reproduction & fertility · 2026Review
- Methodological Approaches for Increasing the Retroviral Transduction Efficiency of Primary NK Cells.Current pharmaceutical design · 2024Article
- Mesenchymal stem cells with p38 mitogen-activated protein kinase interference ameliorate mouse ischemic stroke.Experimental biology and medicine (Maywood, N.J.) · 2023Article
- DEAE-Dextran Enhances the Lentiviral Transduction of Primary Human Mesenchymal Stromal Cells from All Major Tissue Sources Without Affecting Their Proliferation and Phenotype.Molecular biotechnology · 2023Article
- CBX4 Regulates Replicative Senescence of WI-38 Fibroblasts.Oxidative medicine and cellular longevity · 2022Article
- Review
- Article
- Molecular basis of senescence transmitting in the population of human endometrial stromal cells.Aging · 2019Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The unique capacity of mesenchymal stem cells (MSCs) to migrate to the sites of damage, following intravenous transplantation, along with their proliferation and differentiation abilities make them promising candidates for MSC-based gene therapy. This therapeutic approach requires high efficacy delivery of stable transgenes to ensure their adequate expression in MSCs. One of the methods to deliver transgenes is via the viral transduction of MSCs. However, due to low transduction efficiency of MSCs, various polications are used to promote the association of viral particles with membranes of target cells. Among these polications polybrene is the most widely used one. Unfortunately, viral infection in presence of polybrene was shown to negatively affect proliferation rate of stem cells. The molecular mechanism underlying this effect is not yet uncovered. Therefore, the present study aimed to elucidate the mechanism of this phenomenon as well as to develop an effective approach to overcome the negative impact of polybrene on the properties of human endometrium-derived mesenchymal stem cells (hMESCs) during lentiviral infection. We found that the negative effect on proliferation observed during the viral infection in presence of polybrene is mediated by the polycation itself. Furthermore, we revealed that the treatment with polybrene alone led to the p38 MAPK-dependent premature senescence of hMESCs. These findings allowed us to develop an effective strategy to attenuate the negative polybrene impact on the hMESCs properties during lentiviral infection by inhibiting the activity of p38 MAPK. Importantly, the proposed approach did not attenuate the transduction efficiency of hMESCs, yet prevented polybrene-induced senescence and thereby restored the proliferation of the infected cells. These results provide the plausible means to reduce side effects of polybrene during the viral infection of primary cells, particularly MSCs.
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